1a37: Difference between revisions

Revision as of 12:40, 21 February 2008

14-3-3 PROTEIN ZETA BOUND TO PS-RAF259 PEPTIDE

OverviewOverview

14-3-3 proteins bind a variety of molecules involved in signal transduction, cell cycle regulation and apoptosis. 14-3-3 binds ligands such as Raf-1 kinase and Bad by recognizing the phosphorylated consensus motif, RSXpSXP, but must bind unphosphorylated ligands, such as glycoprotein Ib and Pseudomonas aeruginosa exoenzyme S, via a different motif. Here we report the crystal structures of the zeta isoform of 14-3-3 in complex with two peptide ligands: a Raf-derived phosphopeptide (pS-Raf-259, LSQRQRSTpSTPNVHMV) and an unphosphorylated peptide derived from phage display (R18, PHCVPRDLSWLDLEANMCLP) that inhibits binding of exoenzyme S and Raf-1. The two peptides bind within a conserved amphipathic groove on the surface of 14-3-3 at overlapping but distinct sites. The phosphoserine of pS-Raf-259 engages a cluster of basic residues (Lys49, Arg56, Arg60, and Arg127), whereas R18 binds via the amphipathic sequence, WLDLE, with its two acidic groups coordinating the same basic cluster. 14-3-3 is dimeric, and its two peptide-binding grooves are arranged in an antiparallel fashion, 30 A apart. The ability of each groove to bind different peptide motifs suggests how 14-3-3 can act in signal transduction by inducing either homodimer or heterodimer formation in its target proteins.

About this StructureAbout this Structure

1A37 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

ReferenceReference

14-3-3zeta binds a phosphorylated Raf peptide and an unphosphorylated peptide via its conserved amphipathic groove., Petosa C, Masters SC, Bankston LA, Pohl J, Wang B, Fu H, Liddington RC, J Biol Chem. 1998 Jun 26;273(26):16305-10. PMID:9632691

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OCA

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-[[Image:1a37.gif|left|200px]]<br /><applet load="1a37" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="1a37, resolution 3.60&Aring;" />
 '''14-3-3 PROTEIN ZETA BOUND TO PS-RAF259 PEPTIDE'''<br />
 ==Overview==
--3-3 proteins bind a variety of molecules involved in signal, transduction, cell cycle regulation and apoptosis. 14-3-3 binds ligands, such as Raf-1 kinase and Bad by recognizing the phosphorylated consensus, motif, RSXpSXP, but must bind unphosphorylated ligands, such as, glycoprotein Ib and Pseudomonas aeruginosa exoenzyme S, via a different, motif. Here we report the crystal structures of the zeta isoform of 14-3-3, in complex with two peptide ligands: a Raf-derived phosphopeptide, (pS-Raf-259, LSQRQRSTpSTPNVHMV) and an unphosphorylated peptide derived, from phage display (R18, PHCVPRDLSWLDLEANMCLP) that inhibits binding of, exoenzyme S and Raf-1. The two peptides bind within a conserved, amphipathic groove on the surface of 14-3-3 at overlapping but distinct, sites. The phosphoserine of pS-Raf-259 engages a cluster of basic residues, (Lys49, Arg56, Arg60, and Arg127), whereas R18 binds via the amphipathic, sequence, WLDLE, with its two acidic groups coordinating the same basic, cluster. 14-3-3 is dimeric, and its two peptide-binding grooves are, arranged in an antiparallel fashion, 30 A apart. The ability of each, groove to bind different peptide motifs suggests how 14-3-3 can act in, signal transduction by inducing either homodimer or heterodimer formation, in its target proteins.
+-3-3 proteins bind a variety of molecules involved in signal transduction, cell cycle regulation and apoptosis. 14-3-3 binds ligands such as Raf-1 kinase and Bad by recognizing the phosphorylated consensus motif, RSXpSXP, but must bind unphosphorylated ligands, such as glycoprotein Ib and Pseudomonas aeruginosa exoenzyme S, via a different motif. Here we report the crystal structures of the zeta isoform of 14-3-3 in complex with two peptide ligands: a Raf-derived phosphopeptide (pS-Raf-259, LSQRQRSTpSTPNVHMV) and an unphosphorylated peptide derived from phage display (R18, PHCVPRDLSWLDLEANMCLP) that inhibits binding of exoenzyme S and Raf-1. The two peptides bind within a conserved amphipathic groove on the surface of 14-3-3 at overlapping but distinct sites. The phosphoserine of pS-Raf-259 engages a cluster of basic residues (Lys49, Arg56, Arg60, and Arg127), whereas R18 binds via the amphipathic sequence, WLDLE, with its two acidic groups coordinating the same basic cluster. 14-3-3 is dimeric, and its two peptide-binding grooves are arranged in an antiparallel fashion, 30 A apart. The ability of each groove to bind different peptide motifs suggests how 14-3-3 can act in signal transduction by inducing either homodimer or heterodimer formation in its target proteins.
 ==About this Structure==
-A37 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A37 OCA].
+A37 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A37 OCA].
 ==Reference==
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 [[Category: Single protein]]
 [[Category: Fu, H.]]
-[[Category: Liddington, R.C.]]
+[[Category: Liddington, R C.]]
-[[Category: Masters, S.C.]]
+[[Category: Masters, S C.]]
 [[Category: Petosa, C.]]
 [[Category: Pohl, J.]]
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 [[Category: signal transduction]]
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